1. Field of the Invention
The present invention relates to a growth factor-mimicking peptide having an activity of the growth factor, and a composition and a method for improving skin conditions or for treating a wound using the same.
2. Description of the Related Art
Growth hormones secreted from human pituitary glands are known to be directly associated with cell growth and differentiation, and thereby affect a variety of cellular responses, for example including facilitation of growth and development of cartilage or bone, restoration of internal organs such as muscle or liver, regeneration of wounds, and immune responses against infection. Moreover, it has been reported that an amount of growth hormones is gradually reduced due to aging, and the level of growth hormones in a group aged 60 to 69 years is only ¼ compared with that in a group aged 20 to 29 years. Therefore, there have been actively utilized anti-aging hormone therapies which supplement insufficient growth hormones.
Growth hormone is directly bound to a growth hormone receptor in a cell, or induces a secretion of insulin-like growth factor I (IGF-1), leading to activate cellular signal molecules such as JAKs (Janus kinases)/STATs (Signal Transducers and Activators of Transcription), MAPKs (mitogen-activated protein kinases), or PI3K (phosphatidyl-3 kinase). Consequently, it has been supposed that growth hormones promote growth of fibroblasts in hair follicles or skin, and inhibit apoptosis via regulation of a blc-2-like gene, bcl-w. These activities of growth factors have been elucidated by numerous researchers, and various companies have attempted commercialization of growth factors due to their utilization.
Fibroblast growth factor (FGF) is classified into two types, i.e., acidic FGF (aFGF) and basic FGF (bFGF), and both have been reported to be isolated and purified from mammalian brain (Thomas and Gimenez-Gallego, TIBS 11:81-84 (1986)).
Among growth factors, acidic FGF (aFGF) is a protein consisting of 154 amino acids, which is one of major molecules in a biomedical research for tissue restoration and wound healing, for example an activity to regulate growth of animal cells, especially human cells. A mitogen for an acidic fibroblast was first found by Trowell et al. (J. Exp. Biol. 16: 60-70 (1939)) and Hoffman (Growth 4: 361-376 (1940)). In addition, pituitary extracts were found to have a potent mitogenic activity for fibroblasts (Amelin, Proc. Natl. Acad. Sci. USA 70: 2702-2706 (1973)).
Purified aFGF allows numerous cell lines to synthesize DNA and to divide as responses to stimuli, which include primary fibroblasts, vascular and corneal endothelial cells, chondrocytes, myeloblasts, myoblasts, smooth muscle cells, neuroglial cells and neuroblasts (Each et al., Proc. Natl. Acad. Sci. USA 82: 6507-6511 (1985); Kuo et al., Fed. Proc. 44: 695 (1985); Gensburger et al., C.R. Acad. Sc. Paris 303: 465-468 (1986)). Additionally, aFGF not only is a strong mitogenic molecule for vascular endothelial cells but also induces in vivo growth of blood vessel (Thomas. et al., Proc. Natl. Acad. Sci. USA 82: 6409-6413 (1985)). The mitogenic activity of purified aFGF may be also utilized in facilitation of wound healing (Thomas, U.S. Pat. No. 4,444,760).
Meanwhile, keratinocyte growth factor (KGF) is a protein consisting of 163 amino acids, and accelerates division of epithelial cells, contributing to rapid regeneration of several wounds. KGF affects various cell types as a member of fibroblast growth factor family. KGF plays a pivotal role in treatment of cell injuries generated by several causes including adhesion between cells, cell division and aging. In addition, KGF essentially functions as a bridge between cell generations in early stage of hair growth. In addition to improvement in skin elasticity, promotion of hair growth and acceleration of wound healing, KGF may be utilized as various uses.
Likewise, transforming growth factor (TGF) is a cytokine which has an essential activity for growth and differentiation of skin cells in a deep site of skin to maintain the skin very young and health. For example, aging cells damaged may be altered to be very healthful cells with higher division activity through transformation and restoration. TGF treats damaged cells, and thus a scar formation in a tissue may be prevented. TGF binds to an EGF receptor, leading to increase synthesis of a basement membrane protein and to stimulate growth of endothelial cells. TGF may exert several efficacies besides enhancement in skin elasticity, promotion of hair growth, acceleration of wound healing and induction of anti-aging environment.
For mass production of the above-mentioned growth factors, many researchers have made intensive researches on production of the recombinant protein using E. coli expression systems. However, these preparations are encountered to need of time- and cost-consuming refolding process and of complex purification process to remove E. coli-originated contaminants. To be free from such shortcomings, growth factor-like peptides have been prepared by solid phase synthesis methods. For instance, U.S. Pat. No. 5,473,054 filed by Jameson et al. discloses that JB2 (corresponding to amino acid 29-38 of IGF-1) and JB1 (corresponding to amino acid 61-70) fragment have cell proliferation potential and the enantiomer of JB1, JB3 has inhibitory activity to IGF-1. WO 03/048192 filed by Teruo et al. teaches that each of the peptide fragment of IGF-1 consisting of amino acid 33-37 and substance-P derived tetrapeptide exerts complementary efficacy to wound healing. In addition, Kodama et al. reports that the peptide fragment of IGF-1 consisting of amino acid 50-70 has a therapeutic effect to diabetes in mice (Autoimmunity, 37: 481-487 (2004)).
Throughout this application, various patents and publications are referenced, and citations are provided in parentheses. The disclosure of these patents and publications in their entities are hereby incorporated by references into this application in order to more fully describe this invention and the state of the art to which this invention pertains.